Cover Image

Non-Steroidal Anti-Inflammatory Drugs Increase Cisplatin, Paclitaxel, and Doxorubicin Efficacy against Human Cervix Cancer Cells

This study shows that the non-steroidal anti-inflammatory drug (NSAID) celecoxib and its non-cyclooxygenase-2 (COX2) analogue dimethylcelecoxib (DMC) exert a potent inhibitory effect on the growth of human cervix HeLa multi-cellular tumor spheroids (MCTS) when added either at the beginning ("pr...

Full description

Saved in:
Bibliographic Details
Main Authors: Diana Xochiquetzal Robledo-Cadena (Author), Juan Carlos Gallardo-Pérez (Author), Víctor Dávila-Borja (Author), Silvia Cecilia Pacheco-Velázquez (Author), Javier Alejandro Belmont-Díaz (Author), Stephen John Ralph (Author), Betsy Alejandra Blanco-Carpintero (Author), Rafael Moreno-Sánchez (Author), Sara Rodríguez-Enríquez (Author)
Format: Book
Published: MDPI AG, 2020-12-01T00:00:00Z.
Subjects:
article
Online Access:Connect to this object online.
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:This study shows that the non-steroidal anti-inflammatory drug (NSAID) celecoxib and its non-cyclooxygenase-2 (COX2) analogue dimethylcelecoxib (DMC) exert a potent inhibitory effect on the growth of human cervix HeLa multi-cellular tumor spheroids (MCTS) when added either at the beginning ("preventive protocol"; IC<sub>50</sub> = 1 ± 0.3 nM for celecoxib and 10 ± 2 nM for DMC) or after spheroid formation ("curative protocol"; IC<sub>50</sub> = 7.5 ± 2 µM for celecoxib and 32 ± 10 µM for DMC). These NSAID IC<sub>50</sub> values were significantly lower than those attained in bidimensional HeLa cells (IC<sub>50</sub> = 55 ± 9 µM celecoxib and 48 ± 2 µM DMC) and bidimensional non-cancer cell cultures (3T3 fibroblasts and MCF-10A mammary gland cells with IC<sub>50</sub> from 69 to >100 µM, after 24 h). The copper-based drug casiopeina II-gly showed similar potency against HeLa MCTS. Synergism analysis showed that celecoxib, DMC, and casiopeinaII-gly at sub-IC<sub>50</sub> doses increased the potency of cisplatin, paclitaxel, and doxorubicin to hinder HeLa cell proliferation through a significant abolishment of oxidative phosphorylation in bidimensional cultures, with no apparent effect on non-cancer cells (therapeutic index >3.6). Similar results were attained with bidimensional human cervix cancer SiHa and human glioblastoma U373 cell cultures. In HeLa MCTS, celecoxib, DMC and casiopeina II-gly increased cisplatin toxicity by 41-85%. These observations indicated that celecoxib and DMC used as adjuvant therapy in combination with canonical anti-cancer drugs may provide more effective alternatives for cancer treatment.
Item Description:10.3390/ph13120463
1424-8247

Similar Items